Each year, more than 5 million people are treated in US Emergency Departments (EDs) after "minor" motor vehicle collision (MVC) and discharged to home. Persistent pain (most commonly neck pain) develops in 10- 20% of these individuals, with an economic impact of $29 billion per year in the United States alone. Contemporary knowledge regarding the pathogenesis of these common and costly disorders is summarized in biopsychosocial models of post-MVC pain pathogenesis. In recent years, the identification and detailed delineation of mechanisms by which psychological factors contribute to persistent pain development has substantially improved the biopsychosocial model. In contrast, biological factors in the biopsychosocial model remain relatively poorly defined, and are generally limited to estimates of crash severity or initial injury only. Interestingly, increasing evidence indicates that genetic characteristics influencing adrenergic system function may constitute important biological vulnerability factors for the development of posttraumatic pain, and thus may be important to incorporate into the biopsychosocial model. The immediate and ongoing adrenergic response is influenced by the function of important adrenergic system components, including enzymes and transporters that modulate synaptic catecholamine levels and receptors that orchestrate the cellular response. A growing literature documents the ability of these components to influence pain processing, and the investigators'pilot data support the hypothesis that genetic variation in these components affects vulnerability to develop immediate and persistent musculoskeletal pain after minor MVC. The goal of the proposed research, Genetic predictors of acute and chronic musculoskeletal pain after minor MVC, is to assess whether genotypes determining specific adrenergic system processes relevant to pain perception will, when combined with crash-related, psychological, and other factors, improve the prediction of immediate and persistent neck pain symptoms after minor MVC. Patients presenting for evaluation after minor MVC (n = 795) will be recruited in the ED and will receive initial ED evaluation including blood collection for genetic analyses. Patients will then be interviewed 1, 6, and 12 months after the MVC to assess pain outcomes. Pilot data demonstrate the ability of the study team to perform the proposed study and support the potential predictive value of the selected adrenergic system-related genetic factors. The proposed study provides an unprecedented opportunity to develop rich biopsychosocial prediction models of persistent post-MVC neck pain which integrate factors across multiple domains. These models will provide important new knowledge regarding both individual vulnerability characteristics and interactions between genetic and non-genetic factors during the development of post-MVC pain. PUBLIC HEALTH RELEVANCE The proposed study will provide new knowledge regarding both individual vulnerability characteristics and interactions between genetic and non-genetic factors during the development of persistent posttraumatic musculoskeletal pain. Understanding the etiology of musculoskeletal pain disorders is important to the public's health because these disorders are common, cause significant pain and suffering, and are very costly to society.